The University of Maryland Perinatal AIDS Program, through support from NIDA of the study, AIDS Risk in Pregnant IV Drug Users and Their Children, has identified specific behaviors associated with HIV infection in women, differences in pregnancy outcomes associated with drug use and/or HIV infection, specific factors associated with vertical transmission of HIV, methods of early diagnosis in the infant, and characterized the natural history of HIV infection in children. This proposal will extend this work by combining basic scientific with clinical studies to comprehensively address pressing questions regarding these four related areas: pregnancy, vertical transmission, natural history of HIV infection in drug using women, and natural history in their children. We will continue recruitment of drug using pregnant women to permit the application of new molecular biological techniques to assess factors contributing to pregnancy outcome an vertical transmission. We will further our clinical studies of the already established population (120 infected women, 180 at risk children) to determine the effects of continuing drug use and/or repeat pregnancies on HIV disease progression in women and the natural history of HIV infection in children. More sensitive drug testing procedures (urine, meconium) will establish the relationship of at risk behaviors (as assessed by the ALIVE questionnaire) and specific drug usage to health, HIV infection, immune function, viral load, vertical transmission, and disease progression. We will also examine the effects of specific drugs and HIV infection on placental morphology and its relationship to vertical transmission. These clinical studies will be supported by molecular biological approaches (PCR, quantitative co-culture) for quantification of viral load and viral strain identification in maternal and infant blood, and placenta. Immune function in both women and children, as a determinant of vertical transmission and disease progression, will be accurately characterized by expanded cytometric and lymphoproliferative studies and related to specific drug usage.This revised application provides the necessary and critical precision in definitions and data collection, as well as the appropriate virological and immunological assessments. This precision in studies of two very unique, well-defined and homogeneous populations affected by the combination of both drug abuse and HIV infection assure very substantial contributions to the body of knowledge and improved ability for prediction and prevention of vertical transmission and disease progression.